MIAMI BEACH -- An investigational kallikrein inhibitor may hold out hope for people with acute attacks of hereditary angioedema (HAE), a researcher said here.

Action Points

Explain that hereditary angioedema is a rare condition and that this investigational drug seems to produce more rapid resolution of symptoms.

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

MIAMI BEACH -- An investigational kallikrein inhibitor may hold out hope for people with acute attacks of hereditary angioedema (HAE), a researcher said here.

The drug -- dubbed ecallantide -- was associated with a significantly faster time to resolution of symptoms than placebo, according to Marc Riedl, MD, of the University of California Los Angeles.

The difference in speed was especially striking in abdominal and laryngeal attacks, Riedl said in an oral presentation at the annual meeting of the American College of Allergy, Asthma & Immunology.

Peripheral attacks were slower to respond, Riedl said, but are also considered less serious.

The molecule blocks the action of kallikrein, which in patients with the rare condition can become overactive, starting a cascade that leads to production of bradykinin, a peptide that causes the characteristic tissue swelling that is seen with hereditary angioedema.

Between 8,000 and 10,000 people in the U.S. are affected by the condition, which is caused by an autosomal dominant mutation that affects the levels of the so-called C1 inhibitor.

Riedl presented pooled data from two randomized, double-blind Phase III trials of the medication, looking at three outcomes: time to the start of overall improvement, time to sustained improvement, and proportion of patients with complete or near-complete resolution of symptoms

All three endpoints were measured against placebo in the first four hours after the treatment. All of the 143 patients were also given standard therapy, which is simply observation, Riedl said.

"These (outcomes) kind of get at what patients and doctors want to know, which is, 'How long until I feel better?' " Riedl said.

For the first outcome (time to start of overall improvement), Riedl and colleagues found that more patients who were getting the drug felt they had begun to improve during the first four hours, but the median times -- 67 minutes for the drug versus 105 minutes for placebo -- were not significantly different.

On the other hand, the median time to sustained improvement was 98 minutes for those getting the drug, but was not reached among those on placebo, a difference significant at P=0.005.

Finally, 47.1% of patients on the drug reported complete or near-complete resolution of symptoms within the four hours, compared with 26% of those on placebo (P=0.015).

The proportion who said they had complete or near-complete resolution varied by attack site, he said:

For abdominal attacks, 65.2% of those on the drug reported such an outcome, compared with 31.7% for those on placebo (P=0.01).

For peripheral attacks, there was no significant difference within the first four hours.

The bottom line, Riedl said, is that the drug led to "rapid and sustained" relief.

The disease "can really be quality-of-life-diminishing, and even life-threatening," according to John Oppenheimer, MD, of the New Jersey Medical School in Newark, N.J.

Oppenheimer is one of the conference organizers and was not involved in the research.

"Unfortunately, we in the U.S. have not had any good treatments," he said.

Historically, there have been two treatments for the condition -- doses of androgens or fresh frozen plasma -- and neither is popular with patients, according to Gailen Marshall, MD, PhD, of the University of Mississippi Medical Center in Jackson.

Marshall, the editor-in-chief of Annals of Allergy, Asthma, and Immunology, was not involved in the research.

Since the condition preferentially strikes women, "you can imagine what happens when you give chronic androgens to a nice young female," he said. "She doesn't like the beard, she doesn't like the deep voice."

Meanwhile, using plasma is "playing with fire," Oppenheimer said, because in some cases the treatment makes the condition worse.

Marshall said the drug is likely to be used for an acute attack, rather than for prophylaxis.

But for that indication, Oppenheimer said, "it's very exciting for us."

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